ECT continues to be a controversial treatment modality in the management of severe depressive disorders. Much of the difficulty has to do with the possibility of adverse cognitive effects, particularly in the area of memory function. It appears that the risks of such persistent changes may be lower with the use of unilateral nondominant (UL) stimulus electrode placement and brief pulse (P) stimuli. The use of these ECT modifications, however, is controversial, in that their relative efficacy with respect to the more traditional bilateral (BL) electrode placement and sine wave (SW) stimuli continue to be questioned. The issues of both the nature of long-term memory deficits for both types of electrode placement and both types of stimuli and the relative efficacy of these ECT modifications are being addressed in a double-blind prospective study with one-year follow-up. Subjects meet RDC criteria for major depressive disorder endogenous type, using the SADS. This study, which is presently getting underway, is both an extension and a replication of a previous NIMH- and VA-sponsored protocol, which has yielded considerable information regarding these issues. An additional component of the present research is to investigate a variety of hypotheses related to the mechanisms of both therapeutic and adverse effects of ECT, particularly with regard to effects of electrode placement, stimulus waveform and intensity, and characteristics of the induced ictal response. To accomplish these tasks, the extent of therapeutic response and adverse effects, both acutely and over the course of a one-year follow-up period will then be analyzed as a function of neurotransmitter, neuroendocrine, autonomic, and electroencephalographic measures taken during and immediately following the electrically induced seizures.